A serious cause of congestive heart failures is the depressed contraction of the heart muscle. For treating such heart failures, digitalis preparations have been used heretofor. The digitalis preparations have already had a history for 200 years and have become almost a synonym for cardiotonics. However, the digitalis preparations are accompanied by the serious problems in that the toxic-to-therapeutic ratio is narrow and the therapeutic effect is also insufficient.
Cardiotonics acting on sympathetic nerves such as isoprotenol, dopamine, dobutamine, etc. have also been widely used. However, these cardiotonics not only have side effects such as increase in heart rate and arrhythmogenicity, etc., but also exhibit their effect only by an intravenous administration. Accordingly, these cardiotonics cannot be used for treating chronic congestive heart failures.
Thus, attention has now been focused on development of cardiotonics which are effective by oral administration and have a broad therapeutic range and an appropriately long duration of action, and such cardiotonics have been earnestly desired.
The present inventors have investigated compounds having a potent and long acting cardiotonic action by oral administration over long periods of time and finally found that the following compounds can achieve the desired purpose and have thus accomplished the present invention.